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Automated and Integrated Micro-scale Downstream Unit Operations for Monoclonal Antibody Process Development
No full textThe rapid expansion of monoclonal antibody therapeutics has placed increasing pressure on downstream bioprocess development to deliver scalable, efficient, and data-rich strategies. While high throughput process development has transformed chromatographic development, the absence of micro-scale, automation-compatible workflows that also incorporate non-chromatographic steps has limited the scope of current approaches. Without such platforms, it is difficult to generate holistic process understanding, assess inter-step interactions, or support robust design and optimisation at early stages of development.
This thesis set out to design, implement, and evaluate a fully automated micro-scale purification platform capable of reproducing an end-to-end industry-standard model monoclonal antibody downstream process. Benchmark laboratory-scale protocols were successfully translated into micro-scale operations, including capture, viral inactivation, intermediate processing, and polishing, to create an integrated workflow that can operate without manual intervention. The platform was then applied as a rapid development tool, enabling the systematic evaluation of process intermediates, conditions, and outcomes in a high throughput format. By reducing experimental timelines, material requirements, and operator variability, the system provides a reliable surrogate for potential laboratory-scale operations while generating high-quality datasets that can accelerate decision-making. Beyond establishing technical equivalence, the research demonstrates how such micro-scale, automated workflows can unlock new opportunities in process development, optimisation, and design space exploration.
Overall, this work delivers the first fully integrated micro-scale purification platform model for monoclonal antibodies, directly addressing key bottlenecks in downstream development. The platform provides a foundation for digital integration, advanced analytics, and autonomous experimentation, supporting the transition of the biopharmaceutical industry towards the Biopharma 4.0 paradigm
An Anthropology of Global Immunization: Vaccine Politics and Realities in Ethnographic Perspective
No full textAn Anthropology of Global Immunization explores some of the most pressing vaccine concerns of our time, from HPV to COVID-19, HIV and beyond. This edited collection develops a unique anthropological response to the question of global immunization, addressing issues from vaccine hesitancy and conspiracy theories to local biopolitics. The global perspectives in this volume are bound together by critical anthropological themes of nationalism, governance and local biosocial realities. The collection lays a critical foundation to understand vaccine development, implementation and public health policy
Sensory Processing Differences, Mental Health and Mood in Autistic Adults
No full textAutism spectrum disorder (hereafter ‘autism’) is a lifelong neurodevelopmental condition, characterised by persistent differences in social communication and interaction, and restricted, repetitive patterns of behaviours (DSM 5, DSM 5-TR; American Psychiatric Association, 2013; American Psychiatric Association, 2022). Autistic people face high rates of co-occurring mental health challenges across the lifespan, leading to substantial long-term negative impacts on their quality of life (Lai et al., 2019). The current thesis generates novel insights into an autism-specific putative risk factor for various mental health outcomes, namely sensory processing differences (SPDs), which are characterised as the differences in how sensory stimuli are perceived, processed, appraised, and responded to across all sensory modalities (He et al., 2023). SPDs in autism have been investigated for decades (Ben-Sasson et al., 2019) and were more recently identified as one of the top ten research priorities within the autism community. Nevertheless, important knowledge gaps persist in this field. First, despite SPDs being pervasively present in adulthood (Weiland et al., 2020), current sensory research has primarily focused on younger autistic groups. Second, existing sensory research has largely relied on traditional one-off sensory assessments, assuming that sensory processing reflects a relatively stable set of traits (Manning et al., 2025). However, SPDs can fluctuate within an individual depending on personal (e.g., moods) and environmental (e.g., social contexts) factors (Dunn, 1997; MacLennan et al., 2022). Therefore, the dynamic and context-dependent nature of SPDs in autistic people’s everyday lives remain underexplored.
This thesis employs a mixed-methods approach to advance current understanding of SPDs in autistic people. The first chapter provides a general overview of the background of SPDs in autism research. Chapter 2, a systematic review and meta-analysis, provides evidence on the relationships between SPDs and internalising / externalising problems among autistic people. Longitudinal studies (e.g., Green et al., 2012) also demonstrated a predictive relationship, suggesting that SPDs may represent a potential risk factor for later mental health issues. Given the underrepresentation of older autistic adults in this field, Chapter 3 presents a study to further current knowledge of SPDs and the role in mental health across midlife and older autistic adulthood. The second half of the thesis focuses on the implementation of ecological momentary assessment (EMA) with autistic populations. Chapter 4, a systematic review, examines the feasibility and applicability of EMA in autism research. Chapters 5 and 6 describe an EMA study of SPDs, examining the feasibility of using EMA to capture daily sensory experiences among autistic adults (Chapter 5) and exploring momentary SPDs and their relationships with mood states (Chapter 6). The final chapter (Chapter 7) provides an overarching discussion of the findings and implications of the thesis with consideration to future direction, strengths, and limitations
Goal-based representations in decision-making
No full textIn this thesis, I investigate the computational and neural mechanisms by which the brain supports flexible, goal-directed decision-making. Adaptive behaviour requires the brain to construct and maintain internal models that are dynamically shaped by current goals. This work integrates computational modelling, behavioural tasks, and neuroimaging to explore how goals modulate neural representations, how value is encoded, and how confidence influences learning and choice across different cognitive domains.
First, using fMRI and a value-based decision-making task, we demonstrate that a dedicated brain system, centred on the ventromedial prefrontal cortex (vmPFC), encodes the "usefulness" of a stimulus in alignment with a behavioural goal. This suggests that the brain constructs value representations that are highly contextual and goal-dependent, as opposed to simply monetary value or reward. Second, through two virtual maze navigation experiments and computational modelling, we show that participants' spatial representations are best described by a single predictive map, rather than by the creation of separate maps for each goal. Finally, we explore the domain-generality of metacognition and find evidence for a "confidence leak," whereby confidence in one task systematically influences choice behaviour in a subsequent, unrelated task, in a different cognitive domain (i.e, value and perception). This finding suggests a shared, domain-general confidence signal that, while beneficial for cognitive control, can also lead to cross-task biases.
Together, these findings provide a framework for understanding how the brain supports flexible, goal-directed behaviour by dynamically shaping internal models, value signals, and metacognitive evaluations in response to changing goals and environmental demands
Compensation of labour by non-competitive individuals mitigates costs of aggressive succession contest in a tropical social wasp
No full textA paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C
No full textBackground:
Tumor cells typically rely on paracrine stromal signals to guide malignant behavior, yet whether they gain signaling autonomy and thereby reduce microenvironment dependency during metastasis remains unclear.
Methods:
Gremlin 1 (GREM1) and activin A receptor type 1C (ACVR1C) expression levels and cellular distribution were analyzed by immunohistochemistry, immunofluorescence (IF) staining, and single-cell transcriptomics in colorectal cancer (CRC) specimens across stages I–IV. The GREM1–ACVR1C interaction was identified and validated by interaction proteomics, co-immunoprecipitation, IF, and microscale thermophoresis (MST). Functional roles of the GREM1–ACVR1C axis in epithelial–mesenchymal transition (EMT) and metastasis were examined by transcriptomic profiling, pathway analysis, immunoblotting, reverse transcription quantitative PCR (RT–qPCR), scratch and transwell assays, and genetically engineered and xenograft mouse models. An inhibitory peptide targeting the GREM1–ACVR1C interface was designed and evaluated.
Results:
While GREM1 remains restricted to stromal cells in earlier-stage (I–III) CRC, its ectopic expression in tumor epithelium increases markedly in stage IV. Mechanistically, we identify ACVR1C as a direct, high-affinity epithelial receptor for GREM1. Their interaction, independent of canonical transforming growth factor β receptor (TGFβR) and bone morphogenetic protein (BMP) signaling, activates SMAD2/3, which in turn induces the transcription of SNAI1 and GREM1, thereby establishing a self-sustaining autocrine loop that amplifies EMT. Disrupting this loop via stromal GREM1 deletion, epithelial ACVR1C knockdown, kinase inhibition, or a novel GREM1-blocking peptide targeting the GREM1–ACVR1C binding interface significantly impairs CRC metastasis in vivo. Remarkably, while stromal GREM1 is required to initiate this loop, epithelial-derived GREM1 is sufficient to maintain metastatic progression. Clinically, epithelial GREM1 or ACVR1C expression predicts aggressive disease and poor survival.
Conclusions:
Our findings define a paradigm wherein CRC cells hijack the stromal factor GREM1 to establish a tumor-autonomous GREM1–ACVR1C autocrine loop. This loop licenses signaling independence, drives sustained EMT, and represents a novel, actionable vulnerability in advanced CRC
Disentangling the reproductive and metabolic transcriptional responses to diet in Drosophila melanogaster
No full textNutrition significantly influences various life-history traits in organisms, impacting decisions about growth, reproduction, and longevity. Accordingly, previous studies in Drosophila have demonstrated that diet affects transcription regulation, with many genes exhibiting altered expression for example between protein- and carbohydrate-rich diets. It remains challenging, however, to distinguish between metabolic adaptations to the different diets themselves and regulation pertaining to life history responses to nutrient availability. In this study, we explore the transcriptomic responses of virgin and mated flies to changes in nutritional environments, with the aim to differentiate changes in metabolism from changes due to altered reproductive investment. Using RNA-seq, we show that while males only respond to diet, both nutritional conditions and mating status affect gene expression in females. By comparing responses between males and females and virgin and mated flies, we are able to differentiate between basal dietary responses and reproductive adaptations, with the latter involving eight times as many genes as the former. We identify GATA family transcription factors and the heat-shock factor (Hsf) as crucial regulators of diet-dependent reproductive genes. These findings enhance our understanding of the complex interactions between nutrition and reproductive strategies in Drosophila
Becoming a TESOL Practitioner: Disciplinary Languaging and the Socialization of International Students in UK Higher Education
No full textThis article proposes the concept of disciplinary languaging to account for the regulated forms of communication that are characteristic of TESOL master's preparatory programs in the UK. It does so with a view to the effects on the socialization of international students who are attracted by the global promotion of such programs and the promises of English teaching careers but who, nonetheless, are confronted with uncertainties arising from the interplay between the norms and values of TESOL as a discipline taught in UK higher education, on the one hand, and the changing demands of labor markets transnationally, on the other. Drawing on a 1-year ethnographic study, it adopts a trajectory-based sociolinguistic lens and focuses on the case of Lily, a Chinese international student enrolled in a TESOL master's program at a major university in the UK. Lily's engagement with TESOL's disciplinary languaging shaped her own positioning both as a university student and as a Chinese English teacher in significant ways. The analysis shifts the attention away from abstract considerations on what makes a “good” teacher, toward locally emerging practices and logics within which social actors make sense of TESOL preparatory programs and of the process of becoming English teaching practitioners in China
A Framework for Healthcare from the Eye: Oculomics as a Powerful Window to Systemic Health
No full textObjective:
To present a comprehensive framework for integrating oculomics to assess ocular and systemic health, into coordinated healthcare delivery models.
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Design:
Conceptual framework based on current scientific evidence, existing clinical implementations, and expert consensus across ophthalmology, primary care, technology, and population health.
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Participants:
This work synthesizes published evidence and operational experience across diverse care settings.
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Methods:
A narrative synthesis was used to evaluate scientific advances in ocular imaging and visual function testing, multimodal data integration, artificial intelligence (AI), and care-coordination technologies. Implementation insights were incorporated from early deployments of oculomics-enabled programs across clinical and community settings. Four foundation principles were derived to guide ethical, scalable integration of oculomics into care pathways. IRB/Ethics Committee ruled that approval was not required for this study.
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Main Outcome Measures:
Key domains necessary for adopting “Healthcare from the Eye,” including: 1) access to affordable diagnostics, 2) responsible data governance and AI development, 3) patient-care coordination through integrated workflows, and 4) sustainable economic and operational models.
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Results:
Oculomics can support early disease identification, risk stratification, triage, treatment monitoring, and longitudinal care when combined with electronic health records, genetic information, and social determinants of health. Integrating these outputs into clinical workflows enables proactive management of chronic ocular and systemic disease. Early implementations demonstrate improved diagnostic yield, enhanced care coordination, and potential health-system efficiencies. Responsible deployment requires ethical data use, transparent AI, and attention to interoperability, equity and clinician adoption.
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Conclusions:
Healthcare from the Eye provides a structured approach for embedding oculomics into routine clinical care. It can shift health systems from reactive, episodic management toward proactive, continuous, and personalized care. With appropriate guardrails, this framework can improve earlier detection, streamline care pathways, and support population-health efforts across varied clinical environments